Aldehydes with high and low toxicities inactivate cells by damaging distinct cellular targets

Xie, Ming-Zhang; Shoulkamy, Mahmoud I.; Salem, Amir M.H.; Oba, Shunya; Goda, Mizuki; Nakano, Toshiaki; Ide, Hiroshi

doi:10.1016/j.mrfmmm.2016.02.005

Cited by 67 publications

(59 citation statements)

References 49 publications

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“…It would be particularly useful to construct a collection of isogenic knock-in cells with candidate variants using the CRISPR-CAS9 system (Paquet et al 2016). Endogenous aldehydes may include at least several molecular species (Xie et al 2016), and they may induce various types of DNA damage, such as monoadducts, interstrand crosslinks or DNA-protein crosslinks. Which of these actually contributes to FA pathology, and how endogenous aldehydes are generated in cells should be elucidated in the near future.…”

Section: Discussionmentioning

confidence: 99%

Defects in homologous recombination repair behind the human diseases: FA and HBOC

Katsuki

Takata

2016

Endocrine-Related Cancer

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Hereditary breast and ovarian cancer (HBOC) syndrome and a rare childhood disorder Fanconi anemia (FA) are caused by homologous recombination (HR) defects, and some of the causative genes overlap. Recent studies in this field have led to the exciting development of PARP inhibitors as novel cancer therapeutics and have clarified important mechanisms underlying genome instability and tumor suppression in HR-defective disorders. In this review, we provide an overview of the basic molecular mechanisms governing HR and DNA crosslink repair, highlighting BRCA2, and the intriguing relationship between HBOC and FA.

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Section: Discussionmentioning

confidence: 99%

Defects in homologous recombination repair behind the human diseases: FA and HBOC

Katsuki

Takata

2016

Endocrine-Related Cancer

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“…Formaldehyde-mediated genotoxicity is caused by the formation DNA-DNA and DNA-protein cross-links, as well as covalent DNA monoadducts12567. In addition, formaldehyde is able to covalently modify proteins, inhibiting their functions78. The life-threatening damage caused by the broad chemical reactivity of formaldehyde has driven the evolution of mechanisms to detoxify formaldehyde and counteract its detrimental effects2.…”

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confidence: 99%

The mechanism of a formaldehyde-sensing transcriptional regulator

Denby

Iwig

Bisson

et al. 2016

Sci Rep

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Most organisms are exposed to the genotoxic chemical formaldehyde, either from endogenous or environmental sources. Therefore, biology has evolved systems to perceive and detoxify formaldehyde. The frmRA(B) operon that is present in many bacteria represents one such system. The FrmR protein is a transcriptional repressor that is specifically inactivated in the presence of formaldehyde, permitting expression of the formaldehyde detoxification machinery (FrmA and FrmB, when the latter is present). The X-ray structure of the formaldehyde-treated Escherichia coli FrmR (EcFrmR) protein reveals the formation of methylene bridges that link adjacent Pro2 and Cys35 residues in the EcFrmR tetramer. Methylene bridge formation has profound effects on the pattern of surface charge of EcFrmR and combined with biochemical/biophysical data suggests a mechanistic model for formaldehyde-sensing and derepression of frmRA(B) expression in numerous bacterial species.

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“…It is generally accepted that the cytotoxicity of aldehydes is due to the formation of adducts with biologically important macromolecules, which results in their inactivation . Recently, Xie et al have studied the cytotoxic potential of saturated and α,β‐unsaturated aldehydes. The lethal doses that resulted in a cell survival rate of 10% (LD10) were determined using clonogenicity assays after 2 h of aldehyde treatment of Chinese hamster ovary cells.…”

Section: Resultsmentioning

confidence: 99%

Development of an Improved Method to Determine Saturated Aliphatic Aldehydes in Docosahexaenoic Acid‐Rich Oil: A Supplement to p‐Anisidine Value

Zuo

Yang

et al. 2017

Euro J Lipid Sci & Tech

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p‐Anisidine value (AV) is an important and commonly used index to determine the second oxidation statue of edible oils, but it sometimes cannot reflect the concentrations of all the secondary products, such as saturated aldehydes. An improved method for the determination of saturated aliphatic aldehydes (SAA) in docosahexaenoic acid (DHA)‐rich oils is developed in this study. This method reduces the aldehyde 2,4‐dinitrophenylhydrazone adducts (DNPhydrazones) using 2‐picoline borane, which can eliminate the analytical error caused by the isomerism of DNPhydrazone derivatives. The changes of SAA content during the oxidation of DHA‐rich oil is subsequently monitored. Acetaldehyde (168.8 µmol kg−1) and propionaldehyde (78.5 µmol kg−1) are the two main SAAs in fresh oil, and their concentrations increase to 824.8–811.9 µmol kg−1, respectively, after oxidation for 50 h at 80 °C. Furthermore, a Michael addition reaction is found to significantly reduce the AV of oxidized oils, from 172.5 to 11.7. Moreover, the concentration of SAAs shows no significant difference and could clearly identify the low‐quality oil. These results demonstrate that SAA content might be a potential index to identify oxidized oils, which could provide a good supplementary value to the traditional AV index. Practical Applications: The method that has been developed in this study makes it possible to quantify saturated aliphatic aldehydes as markers of oxidation of oils, especially when the panisidine value (AV) cannot correctly assess the levels of secondary products. It could serve as a supplement to the AV index and could be applied to oils, fats, and food products. This work provides quantitative data regarding the amounts of saturated aliphatic aldehydes that can be present in DHA‐rich oils during the oxidation process. An improved method for determinig saturated aliphatic aldehydes (SAA) in docosahexaenoic acid (DHA)‐rich oils is developed. The changes of SAA content during the oxidation of DHA‐rich oil is monitored. Furthermore, a Michael addition reaction is found to significantly reduce the AV of oxidized oils, from 172.5 to 11.7. The concentration of SAAs does not display significant differences and can clearly identify the low‐quality oil. These results demonstrate that the SAA content might be a potential index to identify oxidized oils, which could serve as a good supplement to the AV index.

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Aldehydes with high and low toxicities inactivate cells by damaging distinct cellular targets

Cited by 67 publications

References 49 publications

Defects in homologous recombination repair behind the human diseases: FA and HBOC

Defects in homologous recombination repair behind the human diseases: FA and HBOC

The mechanism of a formaldehyde-sensing transcriptional regulator

Development of an Improved Method to Determine Saturated Aliphatic Aldehydes in Docosahexaenoic Acid‐Rich Oil: A Supplement to p‐Anisidine Value

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